The Association of Common SNPs and Haplotypes in <i>CETP</i> Gene with HDL Cholesterol Levels in Latvian Population

<div><p>The heritability of high-density lipoprotein cholesterol (HDL-C) level is estimated at approximately 50%. Recent genome-wide association studies have identified genes involved in regulation of high-density lipoprotein cholesterol (HDL-C) levels. The precise genetic profile determining heritability of HDL-C however are far from complete and there is substantial room for further characterization of genetic profiles influencing blood lipid levels. Here we report an association study comparing the distribution of 139 SNPs from more than 30 genes between groups that represent extreme ends of HDL-C distribution. We genotyped 704 individuals that were selected from Genome Database of Latvian Population. 10 SNPs from <i>CETP</i> gene showed convincing association with low HDL-C levels (rs1800775, rs3764261, rs173539, rs9939224, rs711752, rs708272, rs7203984, rs7205804, rs11076175 and rs9929488) while 34 SNPs from 10 genes were nominally associated (p<0.05) with HDL-C levels. We have also identified haplotypes from <i>CETP</i> with distinct effects on determination of HDL-C levels. Our conclusion: So far the SNPs in <i>CETP</i> gene are identified as the most common genetic factor influencing HDL-C levels in the representative sample from Latvian population.</p></div

Phylogenetic analysis of full-length amino acid sequences of MC receptors from human, chicken, zebrafish and lamprey

<p><b>Copyright information:</b></p><p>Taken from "Functional characterization of two melanocortin (MC) receptors in lamprey showing orthology to the MC1 and MC4 receptor subtypes"</p><p>http://www.biomedcentral.com/1471-2148/7/101</p><p>BMC Evolutionary Biology 2007;7():101-101.</p><p>Published online 29 Jun 2007</p><p>PMCID:PMC1925065.</p><p></p> The consensus tree was generated by Neighbor-Joining analysis (Phylip 3.6a3). The numbers above the nodes indicate bootstrap replicates. The abbreviations used: Hsa, human; Gga, chicken; Dre, zebrafish and Lfl, lamprey. The accession numbers are listed in "Methods"

Generation of cAMP in response to α-MSH (filled circle), ACTH(1–24) (filled square), MSH-A (open circle), MSH-B (filled triangle) and ACTH (1–31) (open square) for the lamprey MCa receptors expressed in HEK-293 EBNA cells

<p><b>Copyright information:</b></p><p>Taken from "Functional characterization of two melanocortin (MC) receptors in lamprey showing orthology to the MC1 and MC4 receptor subtypes"</p><p>http://www.biomedcentral.com/1471-2148/7/101</p><p>BMC Evolutionary Biology 2007;7():101-101.</p><p>Published online 29 Jun 2007</p><p>PMCID:PMC1925065.</p><p></p> Untransfected cells showed no adenylate cyclase activity in response to ligands (data not shown). The cAMP assay was performed in duplicate and repeated two times with each ligand

Expression of lamprey MCa (a) and MCb (b) receptor mRNA as determined by RT-PCR

<p><b>Copyright information:</b></p><p>Taken from "Functional characterization of two melanocortin (MC) receptors in lamprey showing orthology to the MC1 and MC4 receptor subtypes"</p><p>http://www.biomedcentral.com/1471-2148/7/101</p><p>BMC Evolutionary Biology 2007;7():101-101.</p><p>Published online 29 Jun 2007</p><p>PMCID:PMC1925065.</p><p></p> The tissues, controls and expected sizes of the PCR products are denoted at the top of each figure. Ethidium bromide stained agarose gels are presented on top and autoradiographs of Southern blots, hybridised with gene specific probes, are shown below. The PCR and the hybridization were performed three times with qualitatively similar results

Saturation curves with Scatchard plot and competition curves for the lamprey MCa receptors expressed in HEK-293 EBNA cells

<p><b>Copyright information:</b></p><p>Taken from "Functional characterization of two melanocortin (MC) receptors in lamprey showing orthology to the MC1 and MC4 receptor subtypes"</p><p>http://www.biomedcentral.com/1471-2148/7/101</p><p>BMC Evolutionary Biology 2007;7():101-101.</p><p>Published online 29 Jun 2007</p><p>PMCID:PMC1925065.</p><p></p> The saturation curves (left) were obtained with I-labelled NDP-MSH and the figure shows total binding (filled square) and binding in the presence of 2 μM cold NDP-MSH (filled triangle). The lines represent the computer-modelled best fit of the data assuming that ligands bound to one site. The competition curves (right) for NDP-MSH (filled triangle, pointing up), α-MSH (filled square), β-MSH (open circle), γ-MSH (open diamond), ACTH(1–17) (open square), ACTH(1–24) (filled circle), ACTH(1–39) (x), MTII (filled diamond), HS024 (open triangle, pointing down), MSH-A (filled triangle, pointing down), MSH-B (open triangle, pointing up) and ACTH (1–31) (asterisk) were obtained by using a fixed concentration of approx. 0.6 nM I-labelled NDP-MSH and varying concentrations of the non-labelled competing peptide

The molecular clock analysis of MC1 (open circle), MC2 (filled triangle), MC3 (open square), MC4 (asterisk) and MC5 (filled diamond) receptor subtypes

<p><b>Copyright information:</b></p><p>Taken from "Functional characterization of two melanocortin (MC) receptors in lamprey showing orthology to the MC1 and MC4 receptor subtypes"</p><p>http://www.biomedcentral.com/1471-2148/7/101</p><p>BMC Evolutionary Biology 2007;7():101-101.</p><p>Published online 29 Jun 2007</p><p>PMCID:PMC1925065.</p><p></p> Full-length amino acid sequences were used for the calculations. The distances were calculated with Tree-Puzzle v 5.2. Lamprey MCa (open circle) and MCb (asterisk) are plotted at 564 Myr ago. We used the following divergence times from human: mouse – 90(70), chicken – 310(310), zebrafish – 450(420), dogfish – 528 (420) and lamprey – 564 (525) Myr ago. The corresponding calculated distances were plotted against molecular and fossil data for each receptor subtype separately. The lines are linear regression lines

Amino acid sequence alignment of MC receptors constructed using ClustalW 1

<p><b>Copyright information:</b></p><p>Taken from "Functional characterization of two melanocortin (MC) receptors in lamprey showing orthology to the MC1 and MC4 receptor subtypes"</p><p>http://www.biomedcentral.com/1471-2148/7/101</p><p>BMC Evolutionary Biology 2007;7():101-101.</p><p>Published online 29 Jun 2007</p><p>PMCID:PMC1925065.</p><p></p>8. Putative transmembrane (TM) regions are marked with lines. Black and grey boxes mark conserved and similar amino acid positions, respectively. The abbreviations used: Hsa, human; Gga, chicken; Dre, zebrafish; Lfl, lamprey and Mgl, hagfish. Mgl MCc sequence is partial (119 aa). The accession numbers are listed in "Methods"

Additional file 10: of Many obesity-associated SNPs strongly associate with DNA methylation changes at proximal promoters and enhancers

Replication of the 107 SNP-CpG associations found in blood. *Coefficient of the linear model associated with the obesity-associated SNP: positive for increased methylation with presence of risk allele; coefficients are calculated using M values. Coefficients with a hash symbol correspond to associations with raw p value < 0.05 and coefficients in bold correspond to associations with q value < 0.05. (DOCX 31 kb

Additional file 9: of Many obesity-associated SNPs strongly associate with DNA methylation changes at proximal promoters and enhancers

Correlations between Illumina 450 K and pyrosequence analysis of cg15576492. Methylation at cg15576492, as determined by the Illumina 450 k Chip and expressed as β value, is plotted against methylation at cg15576492, as determined by pyrosequencing and expressed as β value (n = 17). (TIFF 12920 kb

Additional file 1: of Many obesity-associated SNPs strongly associate with DNA methylation changes at proximal promoters and enhancers

Description of the 52 investigated SNPs. SNPs in bold are SNPs for which significant associations with DNA methylation were found. *Number in parenthesis = number of individuals with missing genotypes. (DOCX 108 kb